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ATVB:IMD1-53抑制氧化应激从而减轻腹主动脉瘤

2017-03-14 MedSci MedSci原创

氧化应激在腹主动脉瘤的发生发展中起关键作用,而肾上腺髓质素2(IMD)是氧化应激的调节因子。近期发表于血管权威杂志ATVB上的一项报道研究研究肾上腺髓质素2是否通过抑制氧化应激减轻腹主动脉瘤。

氧化应激在腹主动脉瘤的发生发展中起关键作用,而肾上腺髓质素2(IMD)是氧化应激的调节因子。近期发表于血管权威杂志ATVB上的一项报道研究研究肾上腺髓质素2是否通过抑制氧化应激减轻腹主动脉瘤。

在两种腹主动脉瘤模型:血管紧张素II诱导的ApoE - / - 小鼠和CaCl2孵育诱导的C57BL / 6J小鼠中,IMD1-53显着降低了腹主动脉瘤的发生率和腹主主动脉最大直径。超声检查、苏木精伊红染色和VVG染色显示IMD1-53显着减轻血管紧张素II或CaCl2诱导的腹主动脉扩张及弹性板的断裂和紊乱。机制方面,IMD1-53减轻氧化应激、炎症、血管平滑肌细胞凋亡和基质金属蛋白酶的激活。IMD1-53可抑制氧化还原敏感信号通路的激活,减少烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚基的mRNA和蛋白质表达,并降低腹主动脉瘤小鼠中烟酰胺腺嘌呤二核苷酸磷酸氧化酶的活性。Nox4在人腹主动脉瘤节段和血管紧张素II处理的小鼠血管中显着上调, IMD1-53可显着降低其表达。细胞实验中,IMD小干扰RNA处理血管平滑肌细胞显着增强血管紧张素II诱导的活性氧生成,而Nox4小干扰RNA处理显着抑制活性氧。IMD敲低可进一步增加血管平滑肌细胞的凋亡和炎症发生,且Nox4敲低可逆转这一效应。IMD17-47和蛋白激酶A抑制剂H89预孵育抑制IMD1-53的作用,降低Nox4蛋白水平。

本研究提示IMD1-53可以通过抑制氧化应激减轻腹主动脉瘤。

原始出处:

Lu WW,et al. Intermedin1-53 Attenuates Abdominal Aortic Aneurysm by Inhibiting Oxidative Stress. Arterioscler Thromb Vasc Biol. 2016 Nov;36(11):2176-2190.

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